p53 Allelotypes and Enhanced Detection of Allelic Loss in Ovarian Cancer: Lack of Correlation with Familial and Clinical Factors
To develop a mapping strategy for improved detection of p53 allelic loss associated with ovarian carcinoma, we utilized multiple intragenic polymorphisms and single-strand conformation polymorphism (SSCP) analysis. p53 allelotype distributions were defined for 80 ovarian cancer patients from germ-line DNA. All polymorphic sites studied had polymorphism information content (PIC) rates of greater than 0.25. Tumor loss of heterozygosity (LOH) was determined from informative polymorphisms and migratory shifts on SSCP screening of exons 5-9. Of the four polymorphisms analyzed, the intron 1 (alu) was the most informative (PIC = 0.66). A novel allele of 110 base pairs was found in 4.4% of our ovarian cancer cohort at this site. The intron 3 (16-base pair repeat) and intron 6 (MSP1) polymorphisms were in relative equilibrium; thus, we chose to use only the intron 3 polymorphic site in the mapping strategy. Family cancer history did not influence the allelotype distribution frequencies. Overall, 56 of 61 tumors (91.8%) were informative for allelic loss, and LOH was observed in 66.1%. A reduction to homozygosity at the p53 locus did not correlate with familial or clinical factors. These observations are consistent with the multiple mechanisms by which p53 dysfunction can occur.
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